Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation

Bastian Opitz, Nicolas W J Schröder, Ingo Spreitzer, Kathrin S. Michelsen, Carsten J. Kirschning, Werner Hallatschek, Ulrich Zähringer, Thomas Hartung, Ulf B. Göbel, Ralf R. Schumann

Research output: Contribution to journalArticle

Abstract

Recently Toll-like receptors (TLRs) have been found to be involved in cellular activation by microbial products, including lipopolysaccharide, lipoproteins, and peptidoglycan. Although for these ligands the specific transmembrane signal transducers TLR-4, TLR-2, or TLR-2 and -6 have now been identified, the molecular basis of recognition of lipoteichoic acids (LTAs) and related glycolipids has not been completely understood. In order to determine the role of TLRs in immune cell activation by these stimuli, experiments involving TLR-2-negative cell lines, TLR-expression plasmids, macrophages from TLR-4-deficient C3H/HeJ-mice, and inhibitory TLR-4/MD-2 antibodies were performed. Glycolipids from Treponema maltophilum and Treponema brennaborense, as well as highly purified LTAs from Staphylococcus aureus and Bacillus subtilis exhibited TLR-2 dependence in nuclear factor κB activation and cytokine induction; however, T. brennaborense additionally appeared to signal via TLR-4. Fractionation of the T. brennaborense glycolipids by hydrophobic interaction chromatography and subsequent cell stimulation experiments revealed two peaks of activity, one exhibiting TLR-2-, and a second TLR-4-dependence. Furthermore, we show involvement of the signaling molecules MyD88 and NIK in cell stimulation by LTAs and glycolipids by dominant negative overexpression experiments. In summary, the results presented here indicate that TLR-2 is the main receptor for Treponema glycolipid and LTA-mediated inflammatory response.

Original languageEnglish (US)
Pages (from-to)22041-22047
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number25
DOIs
StatePublished - Jun 22 2001
Externally publishedYes

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Treponema
Toll-Like Receptor 2
Glycolipids
Toll-Like Receptor 4
Toll-Like Receptors
Chemical activation
Toll-Like Receptor 6
Peptidoglycan
Inbred C3H Mouse
Macrophages
Experiments
Bacilli
Fractionation
Chromatography
Bacillus subtilis
Transducers
Hydrophobic and Hydrophilic Interactions
Lipoproteins
Lipopolysaccharides
Staphylococcus aureus

ASJC Scopus subject areas

  • Biochemistry

Cite this

Opitz, B., Schröder, N. W. J., Spreitzer, I., Michelsen, K. S., Kirschning, C. J., Hallatschek, W., ... Schumann, R. R. (2001). Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation. Journal of Biological Chemistry, 276(25), 22041-22047. https://doi.org/10.1074/jbc.M010481200

Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation. / Opitz, Bastian; Schröder, Nicolas W J; Spreitzer, Ingo; Michelsen, Kathrin S.; Kirschning, Carsten J.; Hallatschek, Werner; Zähringer, Ulrich; Hartung, Thomas; Göbel, Ulf B.; Schumann, Ralf R.

In: Journal of Biological Chemistry, Vol. 276, No. 25, 22.06.2001, p. 22041-22047.

Research output: Contribution to journalArticle

Opitz, B, Schröder, NWJ, Spreitzer, I, Michelsen, KS, Kirschning, CJ, Hallatschek, W, Zähringer, U, Hartung, T, Göbel, UB & Schumann, RR 2001, 'Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation', Journal of Biological Chemistry, vol. 276, no. 25, pp. 22041-22047. https://doi.org/10.1074/jbc.M010481200
Opitz B, Schröder NWJ, Spreitzer I, Michelsen KS, Kirschning CJ, Hallatschek W et al. Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation. Journal of Biological Chemistry. 2001 Jun 22;276(25):22041-22047. https://doi.org/10.1074/jbc.M010481200
Opitz, Bastian ; Schröder, Nicolas W J ; Spreitzer, Ingo ; Michelsen, Kathrin S. ; Kirschning, Carsten J. ; Hallatschek, Werner ; Zähringer, Ulrich ; Hartung, Thomas ; Göbel, Ulf B. ; Schumann, Ralf R. / Toll-like Receptor-2 Mediates Treponema Glycolipid and Lipoteichoic Acid-induced NF-κB Translocation. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 25. pp. 22041-22047.
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